Objective: The aim of this study is to determine the effect of Methotrexate (MTX) on glomerular filtration rate (GFR) estimated by radio nucleotide scintigraphy in rheumatoid arthritis (RA) patients. Methods: Thirty adult female RA patients on MTX for at least 2 years with a dose ranging from 15-25 mg/ week intramuscularly were subjected to full history taking, full clinical examination and all laboratory and radiological examination necessary for diagnosis of RA. Eleven RA patients not on MTX, age and sex matched to the patients receiving MTX, served as the control group. GFR was estimated using 99mTc-DTPA. Results: In RA patients on MTX, GFR ranged from 57-128 ml/min with a mean of 83.6 + 2.69. GFR was normal in 9 (30%) patients, mildly affected in 20 (66.7%), moderately affected in 1 (3.3%) patient. In RA patients not on MTX, GFR ranged from 43-115 ml/min with a mean of 89.9 + 7.10. GFR was normal in 8 (72.7%) patients, mildly affected in 1(9.1%), moderately affected in 2 (18.2%) patients. There was a highly significant statistical difference between the studied RA patients & the control group as regards GFR values (P < 0.01). There was a highly significant negative correlation between GFR and patients’ age. There was a significant negative correlation between GFR and MTX dose, MTX duration of treatment and duration of NSAID use (P < 0.05). There was no correlation between GFR and both disease duration and disease activity score. Conclusion: We concluded that MTX, even at low doses, can significantly impair GFR. We, thus, need to exclude renal affection before its use by estimating baseline GFR and creatinine clearance rather than depending on the much less accurate serum creatinine.